Posterior Reversible Encephalopathy Syndrome (PRES)

Audience Emergency medicine residents of all levels Introduction Posterior reversible encephalopathy syndrome (PRES) is a clinically significant cause of seizures, headache, neurologic deficit, and hypertensive emergency that is not uncommon in the emergency department. Posterior reversible encephalopathy syndrome was initially described as a clinical syndrome in 1996.1 It is an important cause of hypertensive emergency that is not often covered in depth in the emergency medicine curriculum since the true incidence and disease process continues to be researched. Populations who are at most risk for PRES include those with chronic hypertension, chronic renal disease, autoimmune disease, and immune suppression.2 Patients with PRES will often present with varied forms of encephalopathy and sometimes even focal neurologic symptoms that would suggest a cerebral vascular accident. These neurologic symptoms can include visual complaints and headache. Seizures are also frequently reported in association with PRES.3 Early identification and appropriate management of PRES decreases morbidity and mortality without chronic neurologic sequelae. The pillars of diagnosis and management can be initiated in the emergency department. This includes a diagnosis made by a thorough history and physical exam and cerebral imaging.4 The mainstay of management is parenteral anti-hypertensives with proper blood pressure monitoring.5 Educational Objectives By the end of the simulation, the learner will be able to: 1) manage an acute seizure 2) discuss imaging modalities to diagnose PRES 3) discuss medical management of PRES. Educational Methods This simulation exercise is meant to be presented as a traditional medium-to-high-fidelity medical simulation case. With minor adjustments, it could be utilized as a low-fidelity case or an oral exam case. Research Methods The educational content and general usefulness of this simulation was evaluated by open verbal (qualitative) feedback from a convenience sample of random participants following a completion of the case and debriefing by a participant group (n=30) of emergency medicine residents at a large 3-year residency training program. Results The overall feedback was positive. Participants felt that it was a good opportunity to practice identifying PRES and managing it in a safe learning environment. They especially appreciated learning more about the pathophysiology of PRES, the high-risk factors for PRES, and management of the condition. Discussion Posterior reversible encephalopathy syndrome, an uncommon condition, presents similar to many other benign and common complaints. It is crucial to be able to differentiate PRES from other causes of headache, visual disturbance, and seizures. It is important to keep PRES in mind when considering hypertensive emergencies. Many PGY-1 residents struggled to diagnose and treat PRES because it was often not on their differential, and this case helped broaden their differential. PGY-2 and PGY-3 were more frequently able to appropriately diagnose and treat PRES in this patient but found the case to be helpful in their decision-making and learning more about PRES pathophysiology. This case and associated high-yield debriefing session were effective for learners of all levels. Topics Posterior reversible encephalopathy syndrome (PRES), altered mental status, seizure, headache, hypertensive emergency.


Linked objectives and methods:
PRES is a rare syndrome that has the potential for neurologic damage. It is becoming ever more recognized due to increased awareness and diagnostic modalities. PRES can have a wide range of clinical presentations but involves a syndrome of hypertension and seizures. It is important for the emergency medicine physician to be able to diagnose and appropriately treat PRES. This simulation will challenge the learners to obtain a thorough history and physical exam (objective 1) in order to develop a differential diagnosis for headache, altered mental status, and seizures (objective 2). As the learners pursue a workup for this patient, they should be able to manage the patient's symptoms of a refractory headache (objective 3) and an acute seizure when the patient has a first-time seizure. PRES could mimic status migrainosus and can cause seizures and sometimes even status epilepticus. Imaging is necessary to diagnose PRES, especially because cerebrovascular accident (stroke) is on the differential diagnosis for the presenting symptoms of the patient. The learners will be able to discuss the different imaging modalities with their benefits and limitations. Once the diagnosis of PRES is made, the learners should be able to initiate appropriate medical management, including appropriate specialty consultation and disposition.
Recommended pre-reading for instructor: •

Results and tips for successful implementation:
This scenario was designed for residents and medical students to diagnose, appropriately treat, and disposition a patient with PRES in the emergency department. This case was designed to be performed using high-fidelity simulation but can also be performed using lower fidelity or as an oral exam case. The case allows learners to work through a broad differential for headache and altered mental status, ultimately treating and diagnosing PRES and seizures as an associated complication.
We conducted a pilot session of this simulation case with approximately 30 emergency medicine residents and medical students in groups of 4-6 which included MS4 medical students and PGY-1 to PGY-3 residents. The educational content and general usefulness of this simulation was evaluated by open verbal (qualitative) feedback from a convenience sample of random participants following a completion of the case and debriefing by a participant group (n=30) of emergency medicine residents at a large 3-year residency training program. Five resident participants and 2 medical students at random provided the most useful feedback for this simulation case rather than about simulation in general ( Table 1).
The case was challenging to the more novice learners (4 th year medical students and PGY-1 residents) who often were unable to make the diagnosis of PRES. Many of them explained that they were not particularly familiar with the diagnosis. The PGY-2 and PGY-3 residents found the case to be useful and were more likely to make the diagnosis and treat PRES appropriately, though many of them also had knowledge gaps identified by this simulation. They were glad for the opportunity to review the pathophysiology and preferred management for PRES. Due to the observations and feedback, we recommend that if interns are given this case, they should be placed in groups with senior residents who may be more familiar with PRES. Participant feedback was generally positive during post-session, and participants did not identify any major areas of change in the simulation scenario. Erythrocyte sedimentation rate (ESR) and C-reactive protein #7 Troponin-I #8 Electrocardiogram (ECG) #9 Chest Radiograph (CXR) #10 Computed tomography (CT) head without contrast #11 Magnetic resonance imaging (MRI) brain without contrast Background and brief information: The scenario takes place in a tertiary/quaternary emergency department. The patient is a 60-year-old woman with a complaint of an unremitting headache.

Initial presentation:
The patient has come from home by private vehicle and has been triaged by nursing as an ESI (Emergency Severity Index) level 2. She is next in queue for medical evaluation. She is laying in the stretcher, alert, and in no acute distress.

How the scenario unfolds:
The patient is a 63-year-old woman who is laying in the bed in no acute distress. She has been experiencing a headache all morning. Learners should rapidly assess the patient's airway, breathing, circulation, and for disability. She should be placed on full cardiopulmonary monitors and learners should obtain a full set of vital signs. The patient has stable airway, breathing, circulation, and does not demonstrate acute neurologic deficit. Vital signs are notable for mild tachycardia and severe hypertension. The learners should obtain a full history and cardiovascular-and neurologic-focused physical exam. The patient's history is significant for a renal transplant and hypertension. Her physical exam is non-focal.
The learner is expected to treat her headache pain with headache abortive agents (eg, IV fluids, antihistamines, analgesics, anti-psychotics, magnesium sulfate, anti-emetics, etc.), keeping status migrainosus in their differential diagnosis. Learners should place an IV line and draw laboratory studies which they feel are appropriate. They may even give the patient oxygen, considering a cluster headache in the differential diagnosis.
Regardless of which medications the patient receives, the patient continues to complain of headache. She has a non-provoked, non-sustained general tonic-clonic seizure. Afterwards, she is post-ictal for a brief period. She will not require airway assistance or even antiepileptics, though some learners may be aggressive in prescribing these interventions. This is the first time the patient has ever had a seizure, so learners are expected to pursue emergency brain imaging, which will likely be a computed tomography (CT) scan of the head.
The CT scan will not be concerning for mass lesion, acute intracranial bleed, or ischemic stroke. The learner should recognize the patient's history and hypertension, seizure, and headache clinically suggest posterior reversible encephalopathy syndrome (PRES). They should manage the patient with intravenous antihypertensives (eg, labetalol, nicardipine or nitroprusside) and consider magnetic resonance imaging (MRI) of the brain. The patient's headache will improve with normalized blood pressure measurements. The learner should also consult a neurologic specialist and a critical care physician for an intensive care unit (ICU) admission. Because the patient is having a hypertensive emergency, she should receive an arterial line for adequate blood pressure monitoring.
If the patient does not have appropriate blood pressure management, she will have another general tonic-clonic seizure.
If the MRI brain is obtained, it will show radiographic findings consistent with PRES.
Optional: For senior learners or for improperly managed PRES, the patient may have status epilepticus at the time of her new-onset seizure: a seizure lasting >5 minutes or 2 or more seizures in a 5-minute period without returning to baseline. She would require benzodiazepines and possibly fosphenytoin/phenytoin, valproic acid, propofol, levetiracetam or another antiepileptic drug. She would also require airway assistance with bag valve mask and/or intubation. If symptom treatment initiated: Blood pressure will improve, and patient will have only mild improvement in symptoms (pain score 5/10) If symptom treatment is not initiated: Patient will complain of worsening pain (pain score 7/10) and nurse will ask participants if symptoms can be treated If there is administration of antihypertensives, the blood pressure will improve, but the next step in the case is for the patient to have a seizure, regardless of whether this intervention is initiated

Posterior Reversible Encephalopathy Syndrome (PRES)
Pathophysiology: Three leading hypotheses exist but the pathophysiology remains controversial. 1. Autoregulation Failure: As the upper limit of cerebral autoregulation is exceeded, cerebral blood flow increases with increases in systolic blood pressure (SBP). This cerebral hyper-perfusion causes breakdown of the blood brain barrier. 2. Cerebral Ischemia: The disordered cerebral autoregulation results in local focal vasoconstriction which leads to local ischemia and cytotoxic edema. 3. Endothelial Dysfunction: Underlying cause of PRES leads to toxicity of vascular endothelium and subsequent vasogenic edema and blood brain barrier dysfunction.

Risk Factors:
• Hypertension: Hypertension associated with autoregulatory failure and is thought to be a key factor in the development of PRES. It is thought that acute changes in blood pressure are related to PRES. • Immunosuppressive Therapy: Approximately 50% of PRES patients are on immunosuppressant therapy; most cases are associated with cyclosporine use. • Renal Disease: PRES is often associated with end-stage renal disease and is most associated with lupus nephritis and glomerulonephritis.
Clinical Features: PRES has been noted in patients aged 2 to 90 years, but is most commonly described in young to middle-aged females. Clinical features vary significantly but most often start with neurological symptoms.
• Headache: Constant, nonlocalized, and frequently refractory to analgesics and other typical migraine abortive agents • Altered Consciousness: Ranging from somnolence to agitation, or coma Radiographic Findings: Radiographic imaging is the gold-standard of diagnosis • CT Scan: Classically, white matter edema is present in the posterior cerebral hemispheres often with cerebellar or brainstem involvement. Importantly, the white matter edema is not localized to a single vascular territory. It is not uncommon for a CT scan without contrast to be read as "normal." MRI: Classically, shows focal areas of increased signal on T1 weighted MRI with leptomeningeal signal enhancement, which is thought to be indicative of blood-brain barrier disruption. Fluid-attenuated inversion recovery (FLAIR) sequences show focal but usually symmetric hemisphere vasogenic edema involving white matter. The severity of presentation has not been shown to correlate with the severity of edema seen on MRI.